Fibronectin is a polymorphic glycoprotein found in plasma, other body fluids, in basement membranes (basal laminae), connective tissue stroma, and vascular walls in vertebrates. From this distribution and the known interactions of fibronectin it seems very likely that fibronectin is important for the orderly depostion of intercellular matrix and in anchoraging positioning normal parenchymal cells. Several types of adherent cells in culture synthesize large quantities of fibronectin and form a fibrillar pericellular matrix composed of fibronectin, procollagen and proteoglycans. Loss of pericellular fibronectin/collagen matrix in transformation represents the largest known difference between normal and transformed adherent cells in culture. The distribution of fibronectin suggests that local and metastatic spreading of tumor involved invasion through fibronectin-containing matrices. The purpose of our study is to 1) identify and quantitate the different forms of fibronectin in cultures of normal and transformed cells and in pathological conditions in vivo 2) to characterize the role of fibronectin in activation of connective tissue, 3) to detail the chemical and structural properties of the pericullular matrix and determine the role of fibronectin in cell adhesion, 4) to characterize the bound and released forms of fibronectin from normal and transformed cells to elucidate the mechanism of fibronectin binding, and 5) to characterize the interaction of malignant cells with fibronectin and other matrix components. Methodology of cell biology, studies on cell transformation, molecular biology, protein chemistry and immunochemistry is in use. We also have good access to clinical material. Further information on fibronectin structure and function may contribute to our understanding of pathogenesis of atherosclerosis and various forms of fibrotic lesions. Study of the abnormal interaction of transformed cells with fibronectin may yield insight into mechanisms of malignant behavior and in the invasive properties of neoplastic cells in general.